LYS-SAF302 Granted IND Clearance for Phase II-III Trial in MPS IIIA


Previously, in a 5-year phase I-II trial, the rAAV vector serotype rh.10 showed promising safety data.

Dr Sophie Olivier

Sophie Olivier, MD, the chief medical officer of Lysogene

Sophie Olivier, MD

The FDA has granted an Investigational New Drug (IND) clearance of a phase II-III clinical trial of LYS-SAF302 (AAVance, Lysogene) for the treatment of Mucopolysaccharidosis Type IIIA (MPS IIIA), also known as Sanfilippo syndrome type A.

MPS IIIA, a severe, lethal, and progressive disorder of the central nervous system caused by SGSH gene mutation, has no approved treatments. The agent acts on the genetic mutation by introducing a healthy copy of SGSH, thus allowing the production of the missing enzyme to slow or halt disease progression.

“Following standing interactions with the FDA, we are pleased to announce full alignment with the Agency on the non-clinical, clinical, regulatory and manufacturing dimensions of our Phase II-III study in the MPS IIIA,” Sophie Olivier, MD, the chief medical officer of Lysogene, said in a statement.1 “Also, the past months were important from a manufacturing perspective resulting in the successful production of LYS-SAF302 and product release to support the demands of the phase II-III clinical trial.”

Previously, in a phase I-II trial, the therapy showed promising safety data over the course of 5 years.2 Additionally, the therapy was well-tolerated, and no biological signs of any toxicity related to the treatment arose. Infectious and adverse events associated with LYS-SAF302 were also absent from the cohort. Although the efficacy analysis from the trial was preliminary, brain atrophy was revealed to be stable in half the patients and increased in the other half. Based on neuropsychological evaluations, behavior, attention, and sleep were shown to be moderately improved in 3 patients, with the youngest of the 4 patients being deemed most likely to show a neurocognitive benefit.

LYS-SAF302 has also previously received Orphan Drug Designation from both the FDA and the EMA, with the FDA additionally granting the rAAV vector serotype rh.10 a Rare Pediatric Disease Designation.

The phase II-III study (NCT03612869) will assess the therapy’s efficacy in improving or stabilizing the neurodevelopmental state of the disease in 20 patients with MPS IIIA. Recorded in time frames of 6, 12, 18, and 24 months, the primary outcome will be the change from baseline in development quotient (DQ), compared to regression reported in natural history studies. It will be measured by the use of the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) or the Kaufman Assessment Battery for Children, Second Edition (KABC-II), dependent upon each patient’s age and range ability.

Secondary outcome measures include the changes from baseline in the total adaptive behavior composite standard score as measured by the expanded interview Vineland Adaptive Behavior Scales (VABS-II), in patient quality of life using the Infant and Toddler Quality of Life (ITQOL) questionnaire, in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4), in sleep pattern as measured by the Children's Sleep Habits Questionnaire (CSHQ), and in total cortical grey matter volume and white matter volume on magnetic resonance imaging.

“The IND clearance of the Phase II-III study of LYS-SAF302 in MPS IIIA represents a major milestone for the clinical trial planned in four leading U.S. sites and four European sites,” said Karen Aiach, MBA, the founder and chief executive officer of Lysogene, in a statement. “The same design, implementation and operational conduct of the study has also been approved by the European Medicines Agency Pediatric Committee (PDCO), thus allowing a robust, rigorous and consistent multi-national approach.”


1. Lysogene Announces FDA approval of IND Application to Initiate Phase 2-3 Clinical Trial in MPS IIIA [press release]. Paris, France: Lysogene. Published September 5, 2018. Accessed September 5, 2018.

2. Tardieu M, Zérah M, Husson B, et al. Intracerebral administration of


-associated viral vector serotype rh.10 carrying human SGSH and SUMF1 cDNAs in children with Mucopolysaccharidosis Type IIIA Disease: results of

a phase

I/II trial. Hum Gene Ther. 2014;25(6).


: 10.1089/hum.2013.238.

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